Tissue inflammatory responses participate in the pathogenesis of a diversity of conditions, syndromes and disorders including, for example, arthritis and ocular inflammation. An important mediator of inflammation is the DEK protein, an abundant and ubiquitous chromatin protein in multicellular organisms. DEK comprises two DNA binding modules of which one includes a SAP box, a sequence motif that DEK shares with other chromatin proteins. DEK has no apparent affinity to specific DNA sequences, but preferentially binds to super-helical and cruciform DNA, and induces positive supercoils into closed circular DNA (Waldmann T. et al., “The DEK protein—an abundant and ubiquitous constituent of mammalian chromatin”, Gene 343: 1-9, 2004.). DEK has recently been found to play a significant role in inflammatory diseases like arthritis (Mor-Vaknin N. et al., “DEK in synovium of patients with juvenile idiopathic arthritis: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen”, Arthritis Rheum. 63: 556-567, 2011, Mor-Vanknin H. et al., “The DEK nuclear antigen is a secreted chemotactic factor”, Mol Cell Biol 26: 9484-9496, 2006.). Because of the structural motifs of DEK, DEK is not a favorable candidate for traditional small-molecule drug discovery.
Improved methods for treating DEK-mediated arthritis and inflammatory disorders are needed.